A PPAR-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J(2), inhibited gastric mucosal injury induced by ischemia-reperfusion in rats.

INTRODUCTION

Recent studies have demonstrated the anti-inflammatory action of 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)), a derivative of the PGD(2) metabolic pathway. Acute inflammation, including neutrophil activation, plays a critical role in the pathogenesis of ischemia-reperfusion (I/R). The aim of the present study was to determine the effect of 15d-PGJ(2) on I/R-induced gastric mucosal injury in rats.

METHODS

Gastric mucosal damage was induced in male Wistar rats by clamping the celiac artery for 30 min followed by reperfusion. 15d-PGJ(2) (0.01-1.0 mg/kg) was given to the rats intraperitoneally 1 h before the vascular clamping. The area of gastric mucosal erosions (erosion index) was measured. Thiobarbituric acid reactive substances (TBARS) and tissue-associated myeloperoxidase (MPO) activity were measured in the gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The expression of tumor necrosis factor-alpha (TNF-alpha) in gastric mucosa was measured by ELISA. In addition, to elucidate whether the protective effects of 15d-PGJ(2) are related to the activation of the PPAR-gamma receptor, we also investigated the effects of a PPAR-gamma antagonist, GW9662.

RESULTS

After 60 min of reperfusion, the area of gastric erosion index had significantly increased from the mean basal levels. The increase in the erosion index was significantly inhibited by pretreatment with 15d-PGJ(2) in a dose-dependent manner. On the other hand, GW9662 reversed the protective effect of 15d-PGJ(2). The concentration of TBARS and MPO activity in the gastric mucosa were both significantly increased after I/R, and pretreatment with 15d-PGJ(2) significantly reduced these increases. The TNF-alpha content was significantly higher in the I/R group than in the sham-operated group. However, the increase in TNF-alpha was significantly inhibited by pretreatment with 15d-PGJ(2).

CONCLUSIONS

15d-PGJ(2) significantly inhibited the severity of acute gastric mucosal injury induced by I/R in rats through PPAR-gamma-dependent mechanisms. This effect may be due, in part, to a reduction in the infiltration of neutrophils into the gastric mucosa, possibly via the inhibition of inflammatory cytokine.